Bradykinin ("BK") is generated under normal conditions in mammalia by the action of various plasma enzymes such as kallikrein on high molecular weight kininogens. It is widely distributed in mammals, as are its two receptor subtypes, BK.sub.1 and BK.sub.2. The actions of BK at the BK1 receptor include mainly contraction of arterial and venous preparations, although it can cause relaxation of peripheral resistance vessels as well.
Many of the more important functions of BK, as increases in vascular permeability, pain, and vasodilatation, however, are mediated by the BK2 receptor. These effects at the BK.sub.2 receptor are believed to be responsible for BK's role in numerous diseases, such as inflammation, cardiovascular disease, pain, and the common cold. Hence antagonists at the BK.sub.2 receptor should find considerable therapeutic applications. Most of the efforts in this area thus far have been directed at peptidic analogues of the BK structure, some of which have been studied as analgesics and antiinflammatory agents.
It would be desirable if there were provided a non-peptide antagonist of the BK.sub.2 receptor, having a good BK.sub.2 antagonistic activity and a good metabolic stability. A variety of dihydropyridine compounds have been synthesized in the field of antihypertensive agents. However, none of these dihydropyridine compounds have been reported as bradykinin antagonists.